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PD-L1 and PD-L2 differ in their molecular mechanisms of interaction with PD-1.

Abstract : The programmed death-1 (PD-1) molecule is involved in peripheral tolerance and in the immune escape mechanisms during chronic viral infections and cancer. PD-1 interacts with two ligands, PD-L1 and PD-L2. We have investigated the molecular mechanisms of PD-1 interactions with its ligands by surface plasmon resonance and cell surface binding as well as the ability of the two ligands to compete for PD-1 binding. PD-L1 and PD-L2 bound PD-1 with comparable affinities, but striking differences were observed at the level of the association and dissociation characteristics. PD-L1, but not PD-L2, had a delayed interaction reminiscent of a phenomenon of conformational transition. These mechanisms were confirmed by using PD-L1 mAbs that delayed the dissociation of PD-L1 from PD-1. This mechanism was not restricted to PD-1 binding since PD-L1 behaved in a similar manner with its second ligand, CD80. Finally, we could demonstrate that PD-L1 and PD-L2 competed for PD-1 binding and conversely, an antagonist PD-1 mAb blocked both PD-L1 and PD-L2 binding to PD-1 and strongly enhanced T-cell proliferation. These data further emphasize the differential molecular mechanisms of interaction of PD-L1 and PD-L2 with PD-1, and suggest possible new approach for the therapy of chronic infection, cancer and transplantation.
Mots-clés : PD-1 PD-L1 PD-L2
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Contributor : Jacques Nunès Connect in order to contact the contributor
Submitted on : Thursday, June 30, 2011 - 8:39:20 AM
Last modification on : Wednesday, November 24, 2021 - 3:29:10 AM
Long-term archiving on: : Saturday, October 1, 2011 - 2:20:22 AM


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Marguerite Ghiotto, Laurent Gauthier, Nacer Serriari, Sonia Pastor, Alemseged Truneh, et al.. PD-L1 and PD-L2 differ in their molecular mechanisms of interaction with PD-1.. International Immunology, Oxford University Press (OUP), 2010, 22 (8), pp.651-60. ⟨10.1093/intimm/dxq049⟩. ⟨inserm-00475236⟩



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